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Mapping of immunodominant CD4 + T lymphocyte epitopes of hepatitis C virus antigens and their relevance during the course of chronic infection
Author(s) -
Hoffmann Robert M.,
Diepolder Helmut M.,
Zachoval Reinhart,
Zwiebel FranzMaximilian,
Jung MariaChristina,
Scholz Siegfried,
Nitschko Hans,
Riethmüller Gert,
Pape Gerd R.
Publication year - 1995
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840210305
Subject(s) - hepatitis c virus , virology , epitope , immunology , antigen , virus , immune system , interferon , medicine , hepatitis , hepatitis c , pathogenesis , biology
In acute and chronic viral disease the specific response of CD4 + T lymphocytes to certain viral proteins is an essential part of antiviral effector mechanisms. In hepatitis C virus infection, the contribution of the immune system and particularly of CD4 + T lymphocytes to the pathogenesis of disease is unknown. We serially determined the peripheral blood CD4 + T lymphocyte response to several recombinant hepatitis C virus proteins (core, NS3, NS4, NS5) and 17 overlapping synthetic peptides derived from the core sequence over up to 48 months in 43 patients with chronic hepatitis C; of these, 16 had been treated with interferon alfa (IFN). Twelve of 27 untreated patients, 4 of 4 sustained responders to IFN, 7 of 8 patients with a transient response, and 1 of 4 nonresponders showed a proliferative response to hepatitis C virus proteins. The hepatitis C virus core protein was the most immunogenic protein, and fine analysis with peptides indicated amino acids 23 to 42, 66 to 85, and 131 to 150 as immunodominant regions. In a subgroup of nine patients, proliferation assays were performed before or during IFN. In this subgroup, sustained responders but not those with a transient or no response to IFN showed a specific CD4 + immune reaction to hepatitis C viral antigens ( P < .05). Infection with hepatitis C virus genotype 3a was significantly associated with a sustained response to IFN ( P < .05). In general, a CD4 + T lymphocyte response was more common in patients with chronic hepatitis C who responded to interferon‐alpha as compared with nonresponders. Thus a strong CD4 + reaction before and during IFN therapy may be a predictor of sustained response.